How Effective is Ketamine Infusion Therapy for Treatment-Resistant Depression?

What you need to know

• Ketamine infusion therapy is showing promise as a rapid-acting treatment for depression that has not responded to standard antidepressants
• It works differently than traditional antidepressants, providing relief from depressive symptoms within hours rather than weeks
• While effective for many patients, ketamine therapy requires careful medical supervision and is not without potential side effects

A new approach for treatment-resistant depression

For patients struggling with severe depression that has not improved with standard treatments, ketamine infusion therapy is emerging as a potentially game-changing option. This article explores how ketamine therapy works, its effectiveness, and important considerations for patients and families.

What is ketamine and how does it work for depression?

Ketamine was originally developed as an anesthetic medication in the 1960s. More recently, researchers discovered that ketamine given at lower doses can rapidly relieve symptoms of depression, often within hours.

This is very different from traditional antidepressants, which typically take 4-6 weeks to start working. Ketamine appears to work through different mechanisms in the brain compared to standard antidepressants:

• It blocks a receptor in the brain called NMDA, which increases the release of a neurotransmitter called glutamate
• This leads to activation of another receptor called AMPA
• Together, these effects promote the formation of new connections between brain cells (synapses)
• The boost in synaptic connections, especially in areas of the brain involved in mood regulation, is thought to rapidly improve depressive symptoms

Additionally, ketamine may reduce inflammation in the brain and improve communication between certain brain regions involved in emotional processing. Researchers are still working to fully understand all the ways ketamine impacts mood and brain function.

How is ketamine therapy administered?

For depression treatment, ketamine is typically given as an intravenous (IV) infusion in a medical office or clinic setting. A typical protocol involves:

• A dose of 0.5 mg/kg of body weight, infused over 40 minutes
• 6 infusions over 2-3 weeks for the initial acute treatment phase
• Follow-up “booster” infusions as needed to maintain the antidepressant effects

Patients are monitored closely during and after the infusion for any side effects. The dose used for depression is much lower than doses used for general anesthesia.

More recently, a nasal spray form of ketamine (esketamine) was also approved for treatment-resistant depression when used along with an oral antidepressant. However, IV ketamine has been studied more extensively so far.

What does the ketamine experience feel like?

During a ketamine infusion, patients may experience:

• Feeling lightheaded or “floaty”
• Blurred or double vision
• A dreamlike state
• Heightened perceptions (colors/sounds may seem more intense)
• A sense of disconnection from your body
• Rarely, mild anxiety or nausea

These effects typically begin about 20 minutes into the infusion, peak near the end, and resolve within 20-40 minutes after the infusion is complete. Many patients describe the experience as strange but not unpleasant. Relaxing music and dim lighting help most patients stay comfortable during treatment.

How effective is ketamine for depression?

Research has found ketamine infusion therapy to be remarkably effective for many patients with treatment-resistant depression:

• 70-80% of patients experience significant improvement in depressive symptoms
• Effects are often rapid, with many patients feeling better within 24 hours of the first treatment
• Ketamine can quickly reduce suicidal thoughts, which is not typically seen with standard antidepressants

However, the effects of ketamine are generally not permanent. Most patients require ongoing periodic treatments to maintain the benefits. Researchers are still determining the optimal long-term treatment protocols.

Who is a good candidate for ketamine therapy?

Ketamine infusion therapy may be an option for patients who meet the following criteria:

• Diagnosis of major depressive disorder (unipolar or bipolar depression)
• Failed to respond to at least two different antidepressant medications
• No history of psychosis
• No substance abuse in the past 12 months
• No uncontrolled high blood pressure or unstable heart disease

A comprehensive psychiatric evaluation is important to determine if ketamine is an appropriate treatment option.

What are the risks and side effects?

When administered in a controlled medical setting, ketamine therapy is generally well-tolerated. Potential side effects may include:

• Dissociation (feeling detached from your body/surroundings)
• Dizziness
• Nausea
• Increased blood pressure
• Headache
• Blurred vision

These effects are usually mild and resolve quickly after the infusion. More serious risks like bladder problems or cognitive impairment have been seen with long-term ketamine abuse, but are not typically associated with controlled medical use for depression.

Is ketamine therapy covered by insurance?

Coverage for ketamine infusions varies by insurance provider. Many still consider it an experimental treatment and do not provide coverage. Patients often need to pay out-of-pocket, with costs ranging from $400-$800 per infusion on average. The nasal spray form (esketamine) is more likely to be covered by insurance when prescribed for treatment-resistant depression.

Conclusions

• Ketamine therapy offers new hope for patients with severe, treatment-resistant depression
• It can provide rapid relief of depressive symptoms, including suicidal thoughts
• While effective for many patients, it requires medical supervision and is not without potential side effects
• More research is still needed on the long-term effects and optimal treatment protocols

Ketamine represents an important new tool for treating depression, but is not appropriate for all patients. Those considering ketamine therapy should have a thorough evaluation by a qualified psychiatrist to determine if it is a good option for their situation. When used appropriately, ketamine infusions can be life-changing for patients who have not found relief through standard depression treatments.